Differential Structure Stabilizing Effects of Epimeric Heparin Analogs on the newt Acidic Fibroblast Growth Factor

T. Srimathi, T. K. S. Kumar and Chin Yu

Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan


Acidic fibroblast growth factor (FGF-1) is a 15kDa all b-sheet protein with various activities like cell proliferation, cell differentiation, angiogenesis and wound healing. Binding of FGF-1 to heparan sulfate-like proteoglycans is important for activating growth factor mediated signal transduction. In the present study, we have compared the relative binding affinities of Glucose Penta Sulfate (GPS) and its epimer Mannose Penta Sulfate (MPS). The mitogenic and angiogenic activity of MPS bound FGF is found to be higher than that of FGF bound to GPS. Results obtained based on multidimensional NMR in conjunction with various biophysical techniques like Isothermal Titration Calorimetry (ITC), BIAcore, fluorescence spectroscopy and circular dichroism suggest that these epimeric and minimalistic heparin analogs produce differential structure stabilization and functional effects on FGF-1